TODO:
##
## DETECTIVE_Ph2 DETECTIVE_Ph3 GATHER
## 329 522 251
## TQ doses in efficacy analyses:
##
## No Radical Cure PQ15 TQ100 TQ300 TQ50
## 186 265 56 482 55
## TQ600
## 56
## [1] 482
## [1] 7.692307
## [1] 4.929577
## 27 patients were lost to follow-up before 1 month
## 39 patients were lost to follow-up before 4 months
## 125 patients were lost to follow-up before 6 months
##
## No Radical Cure PQ15 TQ100 TQ300 TQ50
## 182 257 56 469 54
## TQ600
## 55
## A total of 634 patients received TQ in the efficacy population with doses varying from 0.5 to 14.3 mg/kg
##
## 0 1
## 775 298
##
## 0 1
## 713 360
## Warning: NAs introduced by coercion
## tqcat tqmgkgtot
## 1 No radical cure 0.000000
## 2 PQ 0.000000
## 3 [0.01,3.75) 1.987331
## 4 [3.75,6.25) 4.893435
## 5 [6.25,8.75) 6.936322
## 6 [8.75,15] 10.696189
## tqcat mean n total
## 1 No radical cure 55.5 101 182
## 2 PQ 22.2 57 257
## 3 [0.01,3.75) 33.7 57 169
## 4 [3.75,6.25) 21.5 79 368
## 5 [6.25,8.75) 7.4 4 54
## 6 [8.75,15] 0.0 0 43
## mean age:
## tqcat age
## 1 No radical cure 35
## 2 PQ 36
## 3 [0.01,3.75) 37
## 4 [3.75,6.25) 36
## 5 [6.25,8.75) 36
## 6 [8.75,15] 33
## SD age:
## tqcat age
## 1 No radical cure 14.1
## 2 PQ 14.4
## 3 [0.01,3.75) 13.4
## 4 [3.75,6.25) 14.2
## 5 [6.25,8.75) 17.2
## 6 [8.75,15] 14.4
## tqcat sex
## 1 No radical cure 50
## 2 PQ 77
## 3 [0.01,3.75) 43
## 4 [3.75,6.25) 95
## 5 [6.25,8.75) 24
## 6 [8.75,15] 9
## tqcat sex
## 1 No radical cure 27
## 2 PQ 30
## 3 [0.01,3.75) 25
## 4 [3.75,6.25) 26
## 5 [6.25,8.75) 44
## 6 [8.75,15] 21
## tqcat weight
## 1 No radical cure 62
## 2 PQ 63
## 3 [0.01,3.75) 72
## 4 [3.75,6.25) 63
## 5 [6.25,8.75) 51
## 6 [8.75,15] 57
## tqcat weight
## 1 No radical cure 12.0
## 2 PQ 12.1
## 3 [0.01,3.75) 20.1
## 4 [3.75,6.25) 8.7
## 5 [6.25,8.75) 13.3
## 6 [8.75,15] 7.3
##
## No radical cure PQ [0.01,3.75) [3.75,6.25) [6.25,8.75) [8.75,15]
## Brazil 55 80 61 105 6 3
## Cambodia 10 8 0 16 2 0
## Colombia 0 5 0 11 0 0
## Ethiopia 14 13 0 18 7 0
## India 9 5 21 8 4 7
## Peru 62 91 56 136 21 18
## Philippines 1 2 0 3 0 0
## Thailand 31 38 31 46 10 15
## Vietnam 0 15 0 25 4 0
##
## No radical cure PQ [0.01,3.75) [3.75,6.25) [6.25,8.75) [8.75,15]
## Brazil 30 31 36 29 11 7
## Cambodia 5 3 0 4 4 0
## Colombia 0 2 0 3 0 0
## Ethiopia 8 5 0 5 13 0
## India 5 2 12 2 7 16
## Peru 34 35 33 37 39 42
## Philippines 1 1 0 1 0 0
## Thailand 17 15 18 12 19 35
## Vietnam 0 6 0 7 7 0
## tqcat logpara0.0% logpara0.25% logpara0.50% logpara0.75%
## 1 No radical cure 30 2173 5470 11856
## 2 PQ 104 1712 4697 10430
## 3 [0.01,3.75) 129 1447 4320 9456
## 4 [3.75,6.25) 102 1431 4174 10101
## 5 [6.25,8.75) 151 1961 5507 12111
## 6 [8.75,15] 200 1692 6143 13313
## logpara0.100%
## 1 66010
## 2 87380
## 3 51175
## 4 99604
## 5 80535
## 6 56100
## tqcat hbday0.1 hbday0.2
## 1 No radical cure 12.9 1.5
## 2 PQ 13.0 1.6
## 3 [0.01,3.75) 12.9 1.8
## 4 [3.75,6.25) 13.2 1.6
## 5 [6.25,8.75) 12.3 1.8
## 6 [8.75,15] 12.6 1.8
For supplementary materials
## Rows: 5248 Columns: 18
## ── Column specification ────────────────────────────────────────────────────────
## Delimiter: ","
## chr (11): #ID, TIME, AMT, ODV, LNDV, AGE, SEX, BW, ACT, COUNTRY, PID
## dbl (7): MDV, BLQ, CMT, EVID, TYPE, VOMIT, STUDY
##
## ℹ Use `spec()` to retrieve the full column specification for this data.
## ℹ Specify the column types or set `show_col_types = FALSE` to quiet this message.
## there are a total of 4389 concentrations above LOQ in 718 patients
## [1] 182 257 169 368 54 43
##
## No radical cure PQ [0.01,3.75) [3.75,6.25) [6.25,8.75) [8.75,15]
## Brazil 55 80 61 105 6 3
## Cambodia 10 8 0 16 2 0
## Colombia 0 5 0 11 0 0
## Ethiopia 14 13 0 18 7 0
## India 9 5 21 8 4 7
## Peru 62 91 56 136 21 18
## Philippines 1 2 0 3 0 0
## Thailand 31 38 31 46 10 15
## Vietnam 0 15 0 25 4 0
## Range of mg/kg weights:
## [1] 0.55 14.29
## Median number of methb measurements is 12 (range 2 to 19)
##
## 0 1
## 775 298
##
## 0 1
## No radical cure 81 101
## PQ 200 57
## [0.01,3.75) 112 57
## [3.75,6.25) 289 79
## [6.25,8.75) 50 4
## [8.75,15] 43 0
## Dose (mg) Rec 4 mths (%) n
## 1 No radical cure 55.5 182.0
## 2 PQ 22.2 257.0
## 3 [0.01,3.75) 33.7 169.0
## 4 [3.75,6.25) 21.5 368.0
## 5 [6.25,8.75) 7.4 54.0
## 6 [8.75,15] 0.0 43.0
CYP2D6
##
## FALSE TRUE
## 716 384
##
## 0 0.5 1 1.5 2
## *1/*1 0 0 0 0 407
## *1/*10 0 0 0 56 0
## *1/*17 0 0 0 34 0
## *1/*3 0 0 3 0 0
## *1/*4 0 0 62 0 0
## *1/*41 0 0 0 27 0
## *1/*5 0 0 24 0 0
## *1/*6 0 0 2 0 0
## *1/*9 0 0 0 10 0
## *10/*10 0 0 35 0 0
## *10/*17 0 0 1 0 0
## *10/*41 0 0 8 0 0
## *17/*17 0 0 3 0 0
## *17/*41 0 0 3 0 0
## *3/*4 3 0 0 0 0
## *3/*9 0 1 0 0 0
## *4/*10 0 1 0 0 0
## *4/*17 0 2 0 0 0
## *4/*4 2 0 0 0 0
## *4/*41 0 7 0 0 0
## *4/*5 3 0 0 0 0
## *4/*9 0 1 0 0 0
## *41/*41 0 0 3 0 0
## *5/*10 0 14 0 0 0
## *5/*41 0 1 0 0 0
## *5/*5 1 0 0 0 0
## *5/*9 0 1 0 0 0
## *9/*41 0 0 1 0 0
## CYP2D6 allele frequencies:
##
## *1 *10 *17 *3 *4 *41 *5 *6 *9
## 72.1 10.5 3.2 0.5 5.8 3.7 3.1 0.1 1.0
##
## 0 0.5 1 1.5 2
## 0 6 0 0 0 0
## 0.25 0 15 0 0 0
## 0.5 3 12 35 0 0
## 0.75 0 0 9 0 0
## 1 0 1 96 0 0
## 1.25 0 0 0 56 0
## 1.5 0 0 5 71 0
## 2 0 0 0 0 407
## Activity Score
## CYP2D6 Genotype 0 0.25 0.5 0.75 1 1.25 1.5 2
## *1/*1 0 0 0 0 0 0 0 407
## *1/*10 0 0 0 0 0 56 0 0
## *1/*17 0 0 0 0 0 0 34 0
## *1/*3 0 0 0 0 0 0 3 0
## *1/*4 0 0 0 0 62 0 0 0
## *1/*41 0 0 0 0 0 0 27 0
## *1/*5 0 0 0 0 24 0 0 0
## *1/*6 0 0 0 0 0 0 2 0
## *1/*9 0 0 0 0 0 0 10 0
## *10/*10 0 0 35 0 0 0 0 0
## *10/*17 0 0 0 1 0 0 0 0
## *10/*41 0 0 0 8 0 0 0 0
## *17/*17 0 0 0 0 3 0 0 0
## *17/*41 0 0 0 0 3 0 0 0
## *3/*4 0 0 3 0 0 0 0 0
## *3/*9 0 0 0 0 1 0 0 0
## *4/*10 0 1 0 0 0 0 0 0
## *4/*17 0 0 2 0 0 0 0 0
## *4/*4 2 0 0 0 0 0 0 0
## *4/*41 0 0 7 0 0 0 0 0
## *4/*5 3 0 0 0 0 0 0 0
## *4/*9 0 0 1 0 0 0 0 0
## *41/*41 0 0 0 0 3 0 0 0
## *5/*10 0 14 0 0 0 0 0 0
## *5/*41 0 0 1 0 0 0 0 0
## *5/*5 1 0 0 0 0 0 0 0
## *5/*9 0 0 1 0 0 0 0 0
## *9/*41 0 0 0 0 1 0 0 0
weight
## country outcome_primary.1 outcome_primary.2
## 1 Brazil 26 156
## 2 Cambodia 50 18
## 3 Colombia 36 11
## 4 Ethiopia 16 25
## 5 India 0 9
## 6 Peru 20 162
## 7 Philippines 0 3
## 8 Thailand 11 56
## 9 Vietnam 7 29
## country outcome_primary.1 outcome_primary.2
## 1 Brazil 35 310
## 2 Cambodia 53 36
## 3 Colombia 25 16
## 4 Ethiopia 25 52
## 5 India 4 54
## 6 Peru 30 384
## 7 Philippines 17 6
## 8 Thailand 19 171
## 9 Vietnam 9 44
## country weight
## 1 Ethiopia 53
## 2 Philippines 53
## 3 Thailand 54
## 4 Cambodia 55
## 5 Vietnam 57
## 6 India 60
## 7 Peru 62
## 8 Colombia 67
## 9 Brazil 70
## There are a total of 9632 mthb measurements in 818 patients
## Between day 0 and day 20 there are 5816 measurements. Median (range) per patient is 7 (1 to 12)
##
## Call:
## lm(formula = log10(day7_mthb) ~ tqmgkgtot, data = pk_summaries)
##
## Residuals:
## Min 1Q Median 3Q Max
## -1.11911 -0.16721 0.00514 0.18448 0.62429
##
## Coefficients:
## Estimate Std. Error t value Pr(>|t|)
## (Intercept) -0.100671 0.024584 -4.095 4.76e-05 ***
## tqmgkgtot 0.065552 0.004891 13.404 < 2e-16 ***
## ---
## Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
##
## Residual standard error: 0.2632 on 648 degrees of freedom
## (72 observations deleted due to missingness)
## Multiple R-squared: 0.2171, Adjusted R-squared: 0.2159
## F-statistic: 179.7 on 1 and 648 DF, p-value: < 2.2e-16
## [1] 17.86515
##
## Call:
## lm(formula = t_12_terminal_rescaled ~ AS_score <= 0.5, data = outcome_dat)
##
## Residuals:
## Min 1Q Median 3Q Max
## -9.754 -1.990 -0.422 1.425 33.434
##
## Coefficients:
## Estimate Std. Error t value Pr(>|t|)
## (Intercept) 18.42601 0.20665 89.166 <2e-16 ***
## AS_score <= 0.5TRUE -0.05197 0.69070 -0.075 0.94
## ---
## Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
##
## Residual standard error: 3.899 on 389 degrees of freedom
## (709 observations deleted due to missingness)
## Multiple R-squared: 1.455e-05, Adjusted R-squared: -0.002556
## F-statistic: 0.005662 on 1 and 389 DF, p-value: 0.9401
## Using all data (n=1073), the odds ratio for recurrence at 4 months for each additional mg/kg of tafenoquine is 0.7 (95% CI 0.65 to 0.76)
## Using all data (n=1073), the odds ratio for recurrence at 4 months for each additional mg/kg of primaquine is 0.63 (95% CI 0.55 to 0.71)
## Using only patients who got a 300 mg dose (n=469), the odds ratio for recurrence at 4 months for each additional mg/kg of tafenoquine is 0.66 (95% CI 0.51 to 0.86)
## Using all patients (n=1073), the odds ratio for recurrence at 6 months for each additional mg/kg of tafenoquine is 0.72 (95% CI 0.67 to 0.77)
## Using all patients (n=1073), the odds ratio for recurrence at 6 months for each additional mg/kg of primaquine is 0.61 (95% CI 0.54 to 0.69)
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